Atherosclerosis is a progressive disease that is characterized by the accumulation of lipids, cholesterol, fibrous constituents, monocytes, and various other inflammatory cells in the arterial wall. Atherosclerosis is one of the major causes of morbidity and mortality in developed countries. The major cause of deaths from heart attacks (86%) and brain aneurysm (45%) are due to vulnerable plaques that rupture suddenly and trigger a blood clot or thrombus that blocks blood flow. Early detection of plaque lesions is the first and necessary step in preventing the lethal consequences of atherosclerosis. Diagnosis of the latent vulnerability of a plaque lesion relies on both tissue structural and chemical compositions. Multimodality intravascular imaging that can provide both structure and molecular information will provide clinicians with a critically important tool for diagnosing vulnerable plaques, monitoring the progression of disease, and evaluating the efficacy of intervention. The broad, long term objective of this proposal is to develop an integrated multimodal intravascular imaging system that combines intravascular ultrasound (IVUS), optical coherence tomography (OCT), and photoacoustic tomography (PAT). The multimodal intravascular imaging system is unique in that it combines the advantages of high spatial resolution of OCT, broad imaging depth of US, and molecular contrast of PAT. The integrated IVUS/OCT/PAT will provide the physician with a powerful tool for imaging, diagnosing, and managing vulnerable plaques. The specific aims are: (1) Develop a high-speed nanosecond fiber laser centered at 1730 nm for PAT imaging with lipid contrast; (2) Develop an integrated IVUS/OCT/PAT imaging catheter; (3) Develop a multimodality imaging system that combines IVUS/OCT/PAT; (4) Demonstrate real-time in vivo multimodality imaging of cardiovascular plaques in rabbit and porcine animal models. The proposed research requires an interdisciplinary team of scientists, engineers, and clinicians. We have assembled such a team: OCT/PAT group (Dr. Chen from BLI at UCI); IVUS/PAT group (Drs. Zhou and Shung from NIH Transducer Resource Center at USC); and Interventional cardiology group (Dr. Patel from Dept. of Cardiology at UCI). The proposed research is expected to have significant impact in the earlier detection, prevention, and treatment of cardiovascular diseases. PHS 398